David P. Leader

A Career in Molecular Biology, Biochemistry and Bioinformatics

I was a doctoral student in Oxford during the time that Hans Krebs was Professor of Biochemistry, so one might expect that I had imbibed intermediary metabolism in my mother’s milk, as it were. Not so: as a chemistry undergraduate it was the discovery of molecular biology that had caused me to jump ship for my D.Phil., during which time I was a member of a sect of heretics that included Henry Harris and John Gurdon. Later in Glasgow, however, I eventually met my nemesis. The biochemists with a classical metabolic education had almost all retired, the younger staff had been trained in more ‘modern’ areas of biology, and so it was assumed that, as I had been around so long, I must be able to lecture on intermediary metabolism.

What doesn’t kill you makes you strong, and after a few years I not only came to enjoy delivering the introductory course on intermediate metabolism, but was able (with the help of my colleague, Les Fixter) to devise an advanced laboratory in bioinformatics, based upon the distinctive metabolism of pathogenic and economically useful micro-organisms. It is in the context of this latter experience — which imbued me with an intellectual fascination for the variations in metabolism that are employed by pathogens — that I have been more than happy to contribute my bioinformatics skills to the parasitology group led by Mike Barrett, who is employing metabolomics to study the effects of drugs on trypanosomes and other parasites.

Pathos

‘Pathos’ is a web facility for analysing raw or processed mass spectrometric data from metabolomics experiments. The key feature of ‘Pathos’ is the ability to display the metabolites identified — and changes in their experimental abundance — in the context of the metabolic pathways in which they occur. The initial presentation is as a textual listing of KEGG areas of metabolism, sorted by occurrence. After inspecting these listings, the user is also able to specify an area of interest and retrieve a corresponding pathway map with identified metabolites highlighted. Relative changes in the abundance of metabolites identified under different experimental conditions are indicated by colour-coding, both in the listings and on the maps, and quantitative bar charts can be generated interactively from either of them by a mouse click.